Abstract Over the last two decades there has been a rapid increase in chronic kidney disease of unknown etiology (CKDu) that has emerged in rural, arid, agricultural lowland regions in multiple countries. These regions report 15 to 20% prevalence among men and women between the ages of 30 to 60. CKDu is a progressive and irreversible disease resulting in renal failure and death unless dialysis or a kidney transplant is available. The primary effort to date has focused on identification of the etiological factors that cause CKDu, but the result of intensive investigation have been frustratingly inconclusive leaving public health officials and agricultural workers with little guidance for preventing the disease. In the absence of an approach to prevention, this proposed research will focus on identifying factors associated with delaying progression of the disease in Sri Lanka, one of the countries hardest hit by the CKDu epidemic. The project will be conducted in a rural endemic area of Sri Lanka and calls for an interdisciplinary study focused on identifying the environmental, behavioral and health care factors that are associated with the rate of progression of CKDu from moderate to more advanced CKDu. The project is a collaboration between the University of Connecticut in the US and the University of Peradeniya in Sri Lanka and involves environmental, social and medical scientists from both institutions. A sample of 300 male and female farmers with moderate CKDu as measured by their serum creatinine level will be generated from a Ministry of Health screening in the study area conducted prior to the initiation of the project and followed by quarterly serum creatinine testing by the project to determine trajectory of progression for the individuals in the study sample. The project objective is to identify the factors in the domains of the environment, behavior and health care that are associated with more rapid or slower CKD progression. The specific aims of this proposed project are to: (1) Assess and monitor agrochemicals in water and soil of the microenvironments of individuals with CKDu; (2) Identify behaviors related to farming including hydration, pesticide and agrochemical use during farming, and non-farming behavior including psychological states, stigma, alcohol and tobacco use; (3) Examine the use of health care by individuals with CKDu including use of allopathic v. non-allopathic (e.g. ayurvedic, healer, spiritualist) care, medication adherence, and co-morbidities; and (4). Increase the capacity of faculty and students from both institutions to conduct interdisciplinary research with regard to CKDu in Sri Lanka and other endemic countries. The proposed study would be the first in Sri Lanka to focus on disease progression and potentially transformative for these affected communities. The project also provides the opportunity for cross-disciplinary, cross-national exchange that can be generate a model for addressing NCDs in Sri Lanka and other countries.